precumin IV

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: precumin IV
• 英文别名: (1E,6E)-1,7-bis[3-methoxy-4-(3-methylbut-2-enoxy)phenyl]-4,4-bis(3-methylbut-2-enyl)hepta-1,6-diene-3,5-dione
• 化学式: C₄₁H₅₂O₆
• 分子量: 640.86
• InChiKey: QZVQQCQYQVEWQY-HBKJEHTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.6
• 重原子数：
  47
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  姜黄素 、 1-溴-3-甲基-2-丁烯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 丙酮 为溶剂， 以37%的产率得到precumin III
  参考文献：
  名称：

  Can Small Chemical Modifications of Natural Pan-inhibitors Modulate the Biological Selectivity? The Case of Curcumin Prenylated Derivatives Acting as HDAC or mPGES-1 Inhibitors

  摘要：

  Curcumin, or diferuloylmethane, a polyphenolic molecule isolated from the rhizome of Curcuma Longa, is reported to modulate multiple molecular targets involved in cancer and inflammatory processes. On the basis of its pan-inhibitory characteristics, here we show that simple chemical modifications of the curcumin scaffold can regulate its biological selectivity. In particular, the curcumin scaffold was modified with three types of substituents at positions C-1, C-8, and/or C-8' [C-5 (isopentenyl, 5-8), C-10 (geranyl, 9-12), and C-15 (farnesyl, 13, 14)] in order to make these molecules more selective than the parent compound toward two specific targets: histone deacetylase (HDAC) and microsomal prostaglandin E-2 synthase-1 (mPGES-1). From combined in silico and in vitro analyses, three selective inhibitors by proper substitution at position 8 were revealed. Compound 13 has improved HDAC inhibitory activity and selectivity with respect to the parent compound, while 5 and 9 block the mPGES-1 enzyme. We hypothesize about the covalent interaction of curcumin, 5, and 9 with the mPGES-1 binding site.

  DOI：

  10.1021/acs.jnatprod.5b00700

文献信息

• Can Small Chemical Modifications of Natural Pan-inhibitors Modulate the Biological Selectivity? The Case of Curcumin Prenylated Derivatives Acting as HDAC or mPGES-1 Inhibitors
  作者：Mehrdad Iranshahi、Maria Giovanna Chini、Milena Masullo、Amirhossein Sahebkar、Azita Javidnia、Mahsa Chitsazian Yazdi、Carlo Pergola、Andreas Koeberle、Oliver Werz、Cosimo Pizza、Stefania Terracciano、Sonia Piacente、Giuseppe Bifulco

  DOI：10.1021/acs.jnatprod.5b00700

  日期：2015.12.24

  Curcumin, or diferuloylmethane, a polyphenolic molecule isolated from the rhizome of Curcuma Longa, is reported to modulate multiple molecular targets involved in cancer and inflammatory processes. On the basis of its pan-inhibitory characteristics, here we show that simple chemical modifications of the curcumin scaffold can regulate its biological selectivity. In particular, the curcumin scaffold was modified with three types of substituents at positions C-1, C-8, and/or C-8' [C-5 (isopentenyl, 5-8), C-10 (geranyl, 9-12), and C-15 (farnesyl, 13, 14)] in order to make these molecules more selective than the parent compound toward two specific targets: histone deacetylase (HDAC) and microsomal prostaglandin E-2 synthase-1 (mPGES-1). From combined in silico and in vitro analyses, three selective inhibitors by proper substitution at position 8 were revealed. Compound 13 has improved HDAC inhibitory activity and selectivity with respect to the parent compound, while 5 and 9 block the mPGES-1 enzyme. We hypothesize about the covalent interaction of curcumin, 5, and 9 with the mPGES-1 binding site.